Chronic joint diseases are a major health problem. The economic burden caused by progressive morbidity, loss of function and disability of these diseases is a challenge to society. The outcome and severity of OA, RA and SpA diseases is determined by the balance in the joint between destructive and homeostatic or reparative pathways. The players in DJD include pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a), prostaglandins, tissue destructive enzymes such as matrix metalloproteinases (MMP) and cathepsins and cells such as osteoclasts. The ultimate goal of treatment in DJD and all chronic diseases is not only the inhibition of excessive tissue destruction, but also restoration of homeostasis and eventually tissue repair.
It is well-established that application of weak, non-thermal electromagnetic fields (“EMF”) can result in physiologically meaningful in vivo and in vitro bioeffects. Time-varying electromagnetic fields, comprising rectangular waveforms, such as pulsing electromagnetic fields (“PEMF”), and sinusoidal waveforms, such as pulsed radio frequency fields (“PRF”) ranging from several Hertz to an about 100 MHz range, are clinically beneficial when used as an adjunctive therapy for a variety of musculoskeletal injuries and conditions.
Beginning in the 1960's, development of modern therapeutic and prophylactic devices was stimulated by clinical problems associated with non-union and delayed union bone fractures. Early work showed that an electrochemical pathway can be a means through which bone adaptively responds to mechanical input. Early therapeutic devices used implanted and semi-invasive electrodes delivering direct current (“DC”) to a fracture site. Non-invasive technologies were subsequently developed using capacitively and inductively coupled electromagnetic fields. These modalities were originally created to provide a non-invasive “no-touch” means of inducing an electrical/mechanical waveform at a cell/tissue level. Clinical applications of these technologies in orthopaedics have led to approved applications by regulatory bodies worldwide for treatment of fractures such as non-unions and fresh fractures, as well as spine fusion. Presently several EMF devices constitute the standard armamentarium of orthopaedic clinical practice for treatment of difficult to heal fractures. The success rate for these devices has been very high. The database for this indication is large enough to enable its recommended use as a safe, non-surgical, non-invasive alternative to a first bone graft. Additional clinical indications for these technologies have been reported in double blind studies for treatment of avascular necrosis, tendinitis, osteoarthritis, wound repair, blood circulation and pain from arthritis as well as other musculoskeletal injuries.
Cellular studies have addressed effects of weak, low frequency electromagnetic fields on both signal transduction pathways and growth factor synthesis. It can be shown that EMF stimulates secretion of growth factors after a short, trigger-like duration. Ion/ligand binding processes at a cell membrane are generally considered an initial EMF target pathway structure. The clinical relevance to treatments of bone repair, for example, is upregulation such as modulation of growth factor production as part of normal molecular regulation of bone repair. Cellular level studies have shown effects on calcium ion transport, cell proliferation, Insulin Growth Factor (“IGF-II”) release, and IGF-II receptor expression in osteoblasts. Effects on Insulin Growth Factor-I (“IGF-I”) and IGF-II have also been demonstrated in rat fracture callus. Stimulation of transforming growth factor beta (“TGF-β”) messenger RNA (“mRNA”) with PEMF in a bone induction model in a rat has been shown. Studies have also demonstrated upregulation of TGF-β mRNA by PEMF in human osteoblast-like cell line designated MG-63, wherein there were increases in TGF-β1, collagen, and osteocalcin synthesis. PEMF stimulated an increase in TGF-β1 in both hypertrophic and atrophic cells from human non-union tissue. Further studies demonstrated an increase in both TGF-β1 mRNA and protein in osteoblast cultures resulting from a direct effect of EMF on a calcium (Ca)/calmodulin (CaM)-dependent pathway. Cartilage cell studies have shown similar increases in TGF-β1 mRNA and protein synthesis from PEMF, demonstrating a therapeutic application to joint repair. More recently it has been shown that PEMF can modulate CaM-dependent nitric oxide (NO) signaling. U.S. Pat. No. 4,315,503 (1982) to Ryaby and U.S. Pat. No. 5,723,001 (1998) to Pilla typify the-research conducted in this field.
However, prior art in this field has not produced electromagnetic signals configured specifically to accelerate the asymmetrical kinetics of the binding of intracellular ions to their associated buffers which regulate the biochemical signaling pathways living systems employ for growth, repair and maintenance. The result is that application of prior art devices, such as BGS devices and PRF devices, requires excessively long treatment times with associated prolonged patient morbidity, equivocal outcomes, and unnecessarily higher health care expenses. Prior art in this field also typically required devices which use unnecessarily high amplitude and power to induce a PEMF signal to a target pathway structure, required unnecessarily long treatment time, and were not portable.
Therefore, a need exists for an apparatus and a method that more effectively modulates biochemical processes that regulate tissue growth and repair, shortens treatment times, and incorporates miniaturized circuitry and light weight applicators thus allowing the apparatus to be portable and, if desired, disposable. A further need exists for an apparatus and method that more effectively modulates biochemical processes that regulate tissue growth and repair, shortens treatment times, and incorporates miniaturized circuitry and light weight applicators that can be constructed to be implantable. A further need exists for an apparatus and method that incorporates the asymmetrical kinetics of ion binding to intracellular buffers to configure electromagnetic waveforms to increase the rate of ion binding and enhance the biochemical signaling pathways living systems employ for growth, repair and maintenance.
In particular, there is a need to treat DJD at the level of the joint and affected tissue, using a portable, wearable, lightweight device/apparatus capable of effecting tissue growth and repair. Described herein are devices that may meet the needs described above.